Is PSD p.Arg845Gln (c.2534G>A) pathogenic?

PSD p.Arg845Gln (c.2534G>A) is classified Uncertain significance in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: ambiguous (0.5285); Very rare (popmax 0.000593%, nfe).

How common is PSD p.Arg845Gln (c.2534G>A) in the general population?

PSD p.Arg845Gln (c.2534G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about PSD p.Arg845Gln (c.2534G>A)?

AlphaMissense predicts ambiguous (score 0.5285) — an in-silico prediction, not a clinical call.

PSD p.Arg845Gln

c.2534G>A · rs1397406971 · VCV2318609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5285	ambiguous
REVEL	0.49	indeterminate
SaProt	LLR -12.04	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 4,026 bp · p 0.00092 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,818 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,390 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PSD
Protein: p.Arg845Gln
Coding: c.2534G>A
MANE Select: NM_002779
dbSNP: rs1397406971
Type: single nucleotide variant
Location: chr10:102404919 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 56.76
Residue 845: the ph domain

Full PSD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSD p.Gly336Ser Benign ★★ same type
PSD p.Leu659= Benign ★★ same type
PSD p.Ala1017Pro Uncertain significance ★ ⚠ same type
PSD p.Ala185Pro Uncertain significance ★ ⚠ same type
PSD p.Ala204Val Uncertain significance ★ ⚠ same type
PSD p.Ala260Val Uncertain significance ★ ⚠ same type
PSD p.Ala311Asp Uncertain significance ★ ⚠ same type
PSD p.Ala457Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/psd-p-arg845gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown